The Host Defense Group of the Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, headed by Michael B. Fessler, MD now enters its fifth year at the NIEHS since inception. We have now published several reports: 1. an original publication that defines a novel role for the nuclear receptor Liver X Receptor in modulation of pulmonary innate immunity (Smoak K et al., Journal of Immunology 2008;180(5):3305-12) 2. an investigation using proteomics that has identified novel events in the response of the macrophage to lipopolysaccharide, an environmental innate immune stimulus (Dhungana S et al., Mol Cell Proteomics 2009;8:201-13) 3. 2 reports identifying novel associations between serum cholesterol and asthma/atopy in the U.S. population, using national survey data (Fessler MB et al., J Allergy Clin Immunol 2009;Fessler MB et al., Allergy 2009). 4. 2 review articles on proteomic methodology (Dhungana S et al., Methods Mol Biol 2009a and 2009b) 5. a review article on the role of Toll like Receptors in metabolic syndrome (Fessler MB et al., Curr Opin Lipidol 2009) 6. a review article on mechanisms of neutrophil recruitment to the lung (Cai et al., Am J Respir Cell Mol Biol 2009, in press). 7. a report describing a novel connection between innate immunity and cholesterol trafficking in macrophages (Smoak K et al., Cell Metabolism 2010). 8. 2 reports describing novel interactions between cholesterol and innate immunity in the lung (Draper DW et al., Am J Respir Crit Care Med 2010;Madenspacher JH et al., J Immunol 2010). In addition, 2 additional collaborative papers have been published that 1) describes a novel role for stearoyl-CoA desaturase in atherosclerosis (Brown JM et al., Art Thromb Vasc Biol 2010;and a role for SIRT1 in regulation of macrophage inflammatory responses (Zhu X et al., J Lipid Res 2010). Additional accomplishments since our last report include receipt of 2 2011 Fellow Awards for Research Excellence by postdoctoral fellow Group members David Draper, Ph.D. and Jim Aloor, Ph.D., delivery by Group member Kathleen Smoak (biologist) of an oral presentation at the 2010 Lipid Maps meeting (San Diego, CA), delivery of several regional research seminars by Dr. Fessler, and Chairing by Dr. Fessler of a Scientific Symposium as well as delivery of a research talk at the 2010 American Thoracic Society International Conference. In addition, substantial data has been collected on 5 active research projects in the laboratory: 1) characterization of apoplipoprotein A-I and apolipoprotein E as regulators of pulmonary host defense;2) characterization of the role of the cholesterol transporter ABCG1 in adaptive immunity in the lung;and 3) proteomic identification of macrophage proteins that are modified with the fatty acid palmitate.